- Proceedings of the National Academy of Sciences of the United States of America
- Published 15 days ago
Oral venom systems evolved multiple times in numerous vertebrates enabling the exploitation of unique predatory niches. Yet how and when they evolved remains poorly understood. Up to now, most research on venom evolution has focused strictly on the toxins. However, using toxins present in modern day animals to trace the origin of the venom system is difficult, since they tend to evolve rapidly, show complex patterns of expression, and were incorporated into the venom arsenal relatively recently. Here we focus on gene regulatory networks associated with the production of toxins in snakes, rather than the toxins themselves. We found that overall venom gland gene expression was surprisingly well conserved when compared to salivary glands of other amniotes. We characterized the “metavenom network,” a network of ∼3,000 nonsecreted housekeeping genes that are strongly coexpressed with the toxins, and are primarily involved in protein folding and modification. Conserved across amniotes, this network was coopted for venom evolution by exaptation of existing members and the recruitment of new toxin genes. For instance, starting from this common molecular foundation, Heloderma lizards, shrews, and solenodon, evolved venoms in parallel by overexpression of kallikreins, which were common in ancestral saliva and induce vasodilation when injected, causing circulatory shock. Derived venoms, such as those of snakes, incorporated novel toxins, though still rely on hypotension for prey immobilization. These similarities suggest repeated cooption of shared molecular machinery for the evolution of oral venom in mammals and reptiles, blurring the line between truly venomous animals and their ancestors.
The strategy in New Zealand (Aotearoa) to eliminate coronavirus disease requires that international arrivals undergo managed isolation and quarantine and mandatory testing for severe acute respiratory syndrome coronavirus 2. Combining genomic and epidemiologic data, we investigated the origin of an acute case of coronavirus disease identified in the community after the patient had spent 14 days in managed isolation and quarantine and had 2 negative test results. By combining genomic sequence analysis and epidemiologic investigations, we identified a multibranched chain of transmission of this virus, including on international and domestic flights, as well as a probable case of aerosol transmission without direct person-to-person contact. These findings show the power of integrating genomic and epidemiologic data to inform outbreak investigations.
Approximately 375,000 deaths during 2020 were attributed to COVID-19 on death certificates reported to CDC (1). Concerns have been raised that some deaths are being improperly attributed to COVID-19 (2). Analysis of International Classification of Diseases, Tenth Revision (ICD-10) diagnoses on official death certificates might provide an expedient and efficient method to demonstrate whether reported COVID-19 deaths are being overestimated. CDC assessed documentation of diagnoses co-occurring with an ICD-10 code for COVID-19 (U07.1) on U.S. death certificates from 2020 that had been reported to CDC as of February 22, 2021. Among 378,048 death certificates listing U07.1, a total of 357,133 (94.5%) had at least one other ICD-10 code; 20,915 (5.5%) had only U07.1. Overall, 97.3% of 357,133 death certificates with at least one other diagnosis (91.9% of all 378,048 death certificates) were noted to have a co-occurring diagnosis that was a plausible chain-of-event condition (e.g., pneumonia or respiratory failure), a significant contributing condition (e.g., hypertension or diabetes), or both. Overall, 70%-80% of death certificates had both a chain-of-event condition and a significant contributing condition or a chain-of-event condition only; this was noted for adults aged 18-84 years, both males and females, persons of all races and ethnicities, those who died in inpatient and outpatient or emergency department settings, and those whose manner of death was listed as natural. These findings support the accuracy of COVID-19 mortality surveillance in the United States using official death certificates. High-quality documentation of co-occurring diagnoses on the death certificate is essential for a comprehensive and authoritative public record. Continued messaging and training (3) for professionals who complete death certificates remains important as the pandemic progresses. Accurate mortality surveillance is critical for understanding the impact of variants of SARS-CoV-2, the virus that causes COVID-19, and of COVID-19 vaccination and for guiding public health action.
To quantify rates of organ specific dysfunction in individuals with covid-19 after discharge from hospital compared with a matched control group from the general population.
Large airbursts, the most frequent hazardous impact events, are estimated to occur orders of magnitude more frequently than crater-forming impacts. However, finding traces of these events is impeded by the difficulty of identifying them in the recent geological record. Here, we describe condensation spherules found on top of Walnumfjellet in the Sør Rondane Mountains, Antarctica. Affinities with similar spherules found in EPICA Dome C and Dome Fuji ice cores suggest that these particles were produced during a single-asteroid impact ca. 430 thousand years (ka) ago. The lack of a confirmed crater on the Antarctic ice sheet and geochemical and 18O-poor oxygen isotope signatures allow us to hypothesize that the impact particles result from a touchdown event, in which a projectile vapor jet interacts with the Antarctic ice sheet. Numerical models support a touchdown scenario. This study has implications for the identification and inventory of large cosmic events on Earth.
Intake of processed foods has increased markedly over the past decades, coinciding with increased microvascular diseases such as chronic kidney disease (CKD) and diabetes. Here, we show in rodent models that long-term consumption of a processed diet drives intestinal barrier permeability and an increased risk of CKD. Inhibition of the advanced glycation pathway, which generates Maillard reaction products within foods upon thermal processing, reversed kidney injury. Consequently, a processed diet leads to innate immune complement activation and local kidney inflammation and injury via the potent proinflammatory effector molecule complement 5a (C5a). In a mouse model of diabetes, a high resistant starch fiber diet maintained gut barrier integrity and decreased severity of kidney injury via suppression of complement. These results demonstrate mechanisms by which processed foods cause inflammation that leads to chronic disease.
The human brain has undergone rapid expansion since humans diverged from other great apes, but the mechanism of this human-specific enlargement is still unknown. Here, we use cerebral organoids derived from human, gorilla, and chimpanzee cells to study developmental mechanisms driving evolutionary brain expansion. We find that neuroepithelial differentiation is a protracted process in apes, involving a previously unrecognized transition state characterized by a change in cell shape. Furthermore, we show that human organoids are larger due to a delay in this transition, associated with differences in interkinetic nuclear migration and cell cycle length. Comparative RNA sequencing (RNA-seq) reveals differences in expression dynamics of cell morphogenesis factors, including ZEB2, a known epithelial-mesenchymal transition regulator. We show that ZEB2 promotes neuroepithelial transition, and its manipulation and downstream signaling leads to acquisition of nonhuman ape architecture in the human context and vice versa, establishing an important role for neuroepithelial cell shape in human brain expansion.
SARS-CoV-2 lineage B.1.1.7, a variant first detected in the UK in September 20201, has spread to multiple countries worldwide. Several studies have established that B.1.1.7 is more transmissible than preexisting variants, but have not identified whether it leads to any change in disease severity2. Here we analyse a dataset linking 2,245,263 positive SARS-CoV-2 community tests and 17,452 COVID-19 deaths in England from 1 September 2020 to 14 February 2021. For 1,146,534 (51%) of these tests, the presence or absence of B.1.1.7 can be identified because of mutations in this lineage preventing PCR amplification of the spike gene target (S gene target failure, SGTF1). Based on 4,945 deaths with known SGTF status, we estimate that the hazard of death associated with SGTF is 55% (95% CI 39-72%) higher after adjustment for age, sex, ethnicity, deprivation, care home residence, local authority of residence and test date. This corresponds to the absolute risk of death for a 55-69-year-old male increasing from 0.6% to 0.9% (95% CI 0.8-1.0%) within 28 days after a positive test in the community. Correcting for misclassification of SGTF and missingness in SGTF status, we estimate a 61% (42-82%) higher hazard of death associated with B.1.1.7. Our analysis suggests that B.1.1.7 is not only more transmissible than preexisting SARS-CoV-2 variants, but may also cause more severe illness.
When vaccines are in limited supply, expanding the number of people who receive some vaccine, such as by halving doses or increasing the interval between doses, can reduce disease and mortality compared with concentrating available vaccine doses in a subset of the population. A corollary of such dose-sparing strategies is that the vaccinated individuals may have less protective immunity. Concerns have been raised that expanding the fraction of the population with partial immunity to SARS-CoV-2 could increase selection for vaccine-escape variants, ultimately undermining vaccine effectiveness. We argue that, although this is possible, preliminary evidence instead suggests such strategies should slow the rate of viral escape from vaccine or naturally induced immunity. As long as vaccination provides some protection against escape variants, the corresponding reduction in prevalence and incidence should reduce the rate at which new variants are generated and the speed of adaptation. Because there is little evidence of efficient immune selection of SARS-CoV-2 during typical infections, these population-level effects are likely to dominate vaccine-induced evolution.
After detection of cases of COVID-19 in Florida in March 2020, the governor declared a state of emergency on March 9,* and all school districts in the state suspended in-person instruction by March 20. Most kindergarten through grade 12 (K-12) public and private schools in Florida reopened for in-person learning during August 2020, with varying options for remote learning offered by school districts. During August 10-December 21, 2020, a total of 63,654 COVID-19 cases were reported in school-aged children; an estimated 60% of these cases were not school-related. Fewer than 1% of registered students were identified as having school-related COVID-19 and <11% of K-12 schools reported outbreaks. District incidences among students correlated with the background disease incidence in the county; resumption of in-person education was not associated with a proportionate increase in COVID-19 among school-aged children. Higher rates among students were observed in smaller districts, districts without mandatory mask-use policies, and districts with a lower proportion of students participating in remote learning. These findings highlight the importance of implementing both community-level and school-based strategies to reduce the spread of COVID-19 and suggest that school reopening can be achieved without resulting in widespread illness among students in K-12 school settings.